Fixed-duration venetoclax plus rituximab (VenR) produces sustained progression-free survival (PFS) in patients with relapsed or refractory chronic lymphocytic leukemia (CLL), particularly in patients with undetectable minimal residual disease (uMRD), according to long-term data published in the Journal of Clinical Oncology.1
Authors of the study provided 4-year data from the phase 3 MURANO trial (ClinicalTrials.gov Identifier: NCT02005471) that evaluated VenR compared with bendamustine plus rituximab (BR) as salvage therapy for patients with CLL. BR or ibrutinib have been used for patients with relapsed or refractory CLL with favorable response rates; however, neither treatment is curative in this patient population. Researchers have looked to fixed-duration therapies with venetoclax to provide a more durable response with lower toxicity.
The MURANO trial compared 2-year fixed-duration VenR to BR in patients with relapsed/refractory CLL. In the trial, 194 patients were assigned to the VenR arm, and 195 were assigned to the BR arm. Previous reports on the trial found that patients receiving VenR had significantly improved overall survival (OS) and PFS compared with patients receiving BR.2 The authors of the current study examined 4-year follow-up data and found a continued PFS benefit for VenR (P <.0001), with a 4-year PFS of 57.3% for VenR vs 4.6% for BR. VenR treatment also conferred an OS benefit, with an OS of 85.3% with VenR vs 66.8% with BR (P <.0001).
Disease progression remains a challenge for patients with relapsed or refractory CLL. A total of 73.1% of patients who did not experience disease progression in the 2-year treatment duration also remained progression-free at 4 years. Patients in each arm who developed disease progression received novel targeted agents. There was a 100% response rate in patients who experienced disease progression after fixed-duration VenR therapy who then received ibrutinib (10 patients). Patients who received a venetoclax-based regimen for disease progression after VenR therapy had a 55% response rate (11 patients).
MRD status at the end of treatment affected the PFS rates for patients, with those who had uMRD attaining the highest PFS rate of 90.3% at 18 months. Patients with low MRD positivity had an 18-month PFS of 64.4% and patients with high MRD positivity had an 18-month PFS of 8.3%.
Genomic complexity (GC) also plays a role in clinical outcome, but VenR still showed superiority even among GC subsets. Patients with fewer driver mutations had higher uMRD rates than patients with 1 or more mutations. The authors suggested further analysis of biomarker subsets, as the representation within the trial of each subset was small.
Overall, the early use of fixed-duration VenR for patients with relapsed or refractory CLL produced a sustained, durable response. Salvage therapy with ibrutinib or venetoclax-based regimen is also effective for patients who go on to develop disease progression.
Disclosures: Some authors have declared affiliations with or received grant support from the pharmaceutical industry. Please refer to the original study for a full list of disclosures.
1. Kater AP, Wu JQ, Kipps T, et al. Venetoclax plus rituximab in relapsed chronic lymphocytic leukemia: 4-year results and evaluation of impact of genomic complexity and gene mutations from the MURANO phase III study. J Clin Oncol. Published online September 28, 2020. doi:10.1200/JCO.20.00948
2. Kater AP, Seymour JF, Hillmen P, et al. Fixed duration of venetoclax-rituximab in relapsed/refractory chronic lymphocytic leukemia eradicates minimal residual disease and prolongs survival: post-treatment follow-up of the MURANO phase III study. J Clin Oncol. 2019; 37:269-277. doi: 10.1200/JCO.18.01580